Process for the production of 1-(m-amidophenyl-) 1-hydroxy-2-methylamidopropane



Patented Get. 27, 1931 barren STATES arser rFicE MAX onnnnm, on DARMSTADT, GERMANY PROCESS FGR THE PRODUCTION OF l-(llE-AMIDOPHENYLQ '1HY'DROXY-fB-METHYLAMIDO- PROPANE No Drawing. Application filed April 26, 1930, Serial No. 447,777, and in Germany May 14, 1929.

It is very well known that 1-phenyl-, 1-keto-2-methylamido-propane is very easily influenced by oxidizing agents. Therefore it could not be foreseen that cold diluted as 5 Well as concentrated nitric acid of a specific gravity of 1, would not have any influence on the above mentioned substance; furthermore it is surprising that very strong nitric acid or mixtures of sulfuric and nitric acid do not destroy the substance, but result,

when applied to the mentioned starting material, in the formation of the mono-nitro derivative of same.

The obtained nitro derivative yields metanitro-benzoic acid when oxidized; therefrom results that the product obtained is l-(mnitrophenyl ,1 keto Q-methylamido propane; this is also proved by the analysis; this product being reduced by any of the well known methods of reduction, e. g. molecular hydrogen in presence of catalysts, results in the product-ion of the 1- (m-amidophenyl-) ,1- hydroxy-Q-methylamido-propane. This latter is important inasmuch as it shows the 25 same properties favourable against defects of respiration as the 1-phenyl-,1-hydroxy-2- methylamido-propane, but is less poisonous for about Examples 50 parts of the nitrate of 1-phenyl-,1-keto- Q-methylamido-propane are added step by step to parts of cooled fuming nitric acid of a specific gravity of 1,5, whereby care should be taken that the temperature does not exceed 10 0.; this may be effected by cooling. After solution has taken place the mixture is poured on ice, whereby the nitrate crystallizes out; the watery solution of the o nitrate is alkalized and the precipitated base taken up with ether and gaseous hydrochloric acid is introduced into the dried etheric solution. By recrystallization from a mixture of alcohol and ether the hydrochloride of 1- (m-nitrophenyL) 1-keto-2-methylamidopropane is obtained in the form of white needles. The nitrate of this base crystallizes out from alcohol in form of'white prismatic needles, which melt at 160-161 under decomposition.

10 parts of the so obtained hydrochloride or nitrate dissolved in 100 parts water-are shed in presence of a platin-catalyst inan atmosphere of hydrogen. During about 20 hours an amount of hydrogen is taken up By dissolving the above-mentioned base in water or alcohol and neutralizing the solution by one or two molecules of hydrochloric acid, evaporating the solutions and crystallizing the residue from a mixture of alcohol and ether, the monoor di-hydrochloric salts are received in the form of white crystalline powders. The first melts at 21%2152 the second one at 239240 (under decomposition).

Claims:

1. A process for the production of 1- (mamidophenyl-),1-hyd1'oxy 2 methylamidopropane which consists in the treatment of a salt of 1-phenyl-,1-keto-2-methylamidopropane with nitric acid of a specific gravity of more than 1,4 separating the so formed nitrate of the nitro derivative by crystallization; isolating the so formed nitric salt of the nitro derivative and reducing it in a suitable way, finally precipitating the 1- (m-amidophenyl ,1 hydroxy-2-metl1ylamido-propane by alkalizing the solution.

2. ,As a new and 'useful product l-(mamidophenyL) l-hydroxy-Q-methylamido- 5 propane y forming white crystalline platesshowing a,

melting point of 107l08,5, being easily soluble in alcohol, soluble in chloroform and Water, more difiicultly soluble in ether, insoluble in petrol-ether the mono-hydrochloric salt of vthe new compound consisting of fine white needlesof a melting point of214215, being very easily sohible in water, more diflicultly soluble in alcohol and insoluble inether; the (ii-hydrochloric salt of the'new compound consisting'aof Whiteneedles of a melting point of 239 2fl0 under decomposi-v tion5 being 'very easily'soluble in ater, more 0 diflicultly soluble in alcohol and insoluble in In testimony whereof I have hereunto signed myname at Frankfort-cin-the-Main this twelfth day of April, 1930. '7 OBERLIN. 

